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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

泛癌分析确定HSPA5的预后分析和免疫浸润

卷 24, 期 1, 2024

发表于: 31 May, 2023

页: [14 - 27] 页: 14

弟呕挨: 10.2174/1568009623666230508111721

价格: $65

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摘要

背景：热休克70kDa蛋白5 (HSPA5)，也称为GRP78，在大多数恶性细胞中广泛表达，并已被证明通过将大多数恶性肿瘤转移到细胞膜上，在大多数恶性肿瘤的扩散中起重要作用。高水平的HSPA5可促进肿瘤生长和迁移，抑制细胞凋亡，与预后密切相关，可作为多种恶性肿瘤的独立预后标志物。因此，利用泛癌症研究来检测HSPA5至关重要，这可能会发现新的癌症治疗靶点。 方法：GTEx和TCGA数据库都提供了HSPA5在不同组织中表达量不同的证据。临床蛋白质组学肿瘤分析联盟(CPTAC)评估了HSPA5蛋白的表达水平，而qPCR研究也评估了某些肿瘤中HSPA5 mRNA的表达。使用Kaplan-Meier方法研究HSPA5如何影响恶性肿瘤的总生存期和无病生存期。采用GEPIA2研究HSPA5表达与肿瘤临床分期的相关性。肿瘤免疫系统相互作用数据库(TISIDB)检测了HSPA5在分子和肿瘤免疫亚型中的表达。从STRING数据库中提取HSPA5共表达基因，并在TIMER数据库中鉴定出33种癌症中HSPA5共表达前5位的基因。进一步的研究检验了肿瘤突变与HSPA5之间的关系。微卫星不稳定性(MSI)和肿瘤突变负荷(TMB)是主要的研究领域。利用TIMER数据库探讨HSPA5 mRNA表达与免疫浸润的关系。此外，通过Linkedomics数据库，我们检测了胶质母细胞瘤中GO和KEGG对HSPA5的富集。最后，利用聚类分析工具进行GSEA功能富集研究。 结果：研究发现，在所有23种肿瘤组织中，HSPA5 mRNA的表达均高于同等正常组织，通过生存图观察到，在大多数癌症中，HSPA5的高表达似乎与不良预后密切相关。在肿瘤临床分期显示图中，HSPA5在大多数肿瘤中均有差异表达。HSPA5与肿瘤突变负荷(TMB)和微卫星不稳定性(MSI)密切相关。癌相关成纤维细胞(CAFs)浸润与HSPA5密切相关，9种免疫亚型恶性肿瘤和7种分子亚型恶性肿瘤也是如此。根据GO和KEGG富集分析结果，HSPA5在GBM中主要参与中性粒细胞介导的免疫和胶原代谢活动。此外，HSPA5及其相关基因的GSEA富集分析表明，HSPA5与肿瘤的免疫环境、细胞分裂和神经系统调节之间存在实质性联系。通过qPCR，我们能够进一步证实在GBM、COAD、LUAD和CESC细胞系中表达增强。 结论：我们的生物信息学研究使我们假设HSPA5可能参与免疫浸润以及肿瘤的生长和进展。此外，我们还发现HSPA5的差异表达与癌症预后不良有关，神经系统、肿瘤免疫微环境和细胞分裂是潜在的影响因素。因此，HSPA5 mRNA和相关蛋白可能被用作一系列恶性肿瘤的治疗靶点和可能的预后标志物。

关键词: 热休克70kDa蛋白5(HSPA5)，癌症相关成纤维细胞，免疫浸润，微卫星不稳定性，肿瘤突变负担，细胞分裂。

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